Patent GB-765849-A (GB)
Title: Improvements in or relating to new aminoalkyl phenyl ethers
Inventor: HEY PETER
Filed: 1953-09-21
Abstract: The invention comprises compounds of the formula: <FORM:0765849/IV(b)/1> in which R1 and R2 are the same or different and are lower alkyl groups or chlorine atoms and R3 is a hydrogen atom or, where one or both of R1 and R3 are lower alkyl groups, a lower alkyl group, A represents a divalent group selected from -CH2-CH2-, <FORM:0765849/IV(b)/2> and R4 and R5 each represent a lower alkyl group (i.e. having up to 6 carbon atoms).  Such compounds are obtainable by reacting a compound of the formula: <FORM:0765849/IV(b)/3> with a compound of the formula Y-Z where X, Y and Z represent atoms or groups such that X will react with Y-Z to form the group: <FORM:0765849/IV(b)/4> or a group readily convertible into such grouping, and in the latter case effecting such a conversion.  "Convertible" groupings include -A-NH2, A.NHR4, -A-Halogen and A1CO.  NR4R5 where A1 represents a group differing from A by a CH2 group.  In the preferred process a phenol: <FORM:0765849/IV(b)/5> is reacted with a dialkylaminoalkyl halide of the formula Hal.A.NR3R4.  Alternative methods are (a) reaction of the appropriate ester with an amine HNR4R5, (b) reduction of the corresponding amide, (c) alkylation of the corresponding primary or secondary amine.  Where A is a branched chain, isomerization may occur during the reaction, the two isomers formed being separable by fractional crystalllization of their hydrochlorides.  The starting materials can be prepared by reaction of the appropriate phenol ArOH with the appropriate basic ester to give Ar-O-A-NHR4 or Ar-O-A-NR4R5. Compounds of the type Ar-O-A-M (where M represents an ester group) are obtained by reacting the phenol with a diester M-A-M.  Compounds of the type Ar-O-A1-CONR4R5 are obtained by reacting the appropriate phenol with an amide ester of the type M-A1-CONR4R5.  In examples: (1) 2 - (b  - dimethylaminoethoxy) - 1 : 3 - dichlorobenzene hydrochloride is prepared by the reaction of 2 : 6-dichlorophenol in aqueous sodium hydroxide solution with b -dimethylaminoethyl chloride hydrochloride; (2) the same product is obtained by reacting the sodium derivative of 2 : 6-dichlorophenol in acetone solution with an ethereal solution of b -dimethylaminoethyl chloride. Similarly obtained are (3) 2-(21-dimethylamino - 11 - methylethoxy) - 1 : 3 - dimethyl benzene hydrochloride (by fractional crystallization from the crude product from 2 : 6-xylenol and 3 - dimethylamino - 2 - chloropropane; (4) a mixture of 2 - (21 - diethylamino - 21-methylethoxy) - 1 : 3 - dimethylbenzene and 2-(21 - diethylamino - 11 - methylethoxy) - 1 : 3-dimethylbenzene (which is separated into its components by fractional crystallization) from 2 : 6-xylenol and 3-diethylamino-2-chloropropane hydrochloride; (5) b  - (2 : 6 - xylyloxy)-ethyldimethylamine and b  - (2 : 6 - xylyloxy) ethyldiethylamine, which are converted to hydrobromides.  The two latter compounds can also be prepared by reacting the corresponding aryloxyethyl bromide with excess ethereal dimethylamine or diethylamine in a sealed ampoule at room temperature.  The Provisional Specification also describes the reaction of 2 : 6-xylenol and 2 : 4 : 6-mesitol with 1 : 2-dibromoethane to give b -(2 : 6-xylyloxy)-ethyl bromide and b -(2 : 4 : 6-mesityloxy)-ethyl bromide respectively. Specification 687,189 is referred to.